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Biomedical subjects

K Shima

Publications and source records attributed to K Shima.

At least 199 records · Page 11Linked to original sources

Sexual difference in the incidence of diabetes mellitus in Otsuka-Long-Evans-Tokushima-Fatty rats: effects of castration and sex hormone replacement on its incidence.

The incidence of non-insulin-dependent diabetes mellitus in a model rat (Otsuka-Long-Evans-Tokushima Fatty [OLETF]) has been shown to be much higher in males than in females. To evaluate the role of sex hormones in the development of diabetes in this model, we performed biochemical and morphological studies on the effects of castration and sex hormones on the development of non-insulin-dependent diabetes mellitus in these rats. The rats were randomly assigned to six groups of 10 rats each, three groups of males and three of females. Two of the male groups and two of the female groups were castrated at 5 weeks of age, and the third male and female groups received sham operations. From 9 to 30 weeks of age, one group of castrated males received testosterone enanthate (1 mg-wk-1) and one group of castrated females received estradiol valerate (1 mg.wk-1). The other castrated groups received an equal volume of vehicle only. At 30 weeks of age, the cumulative incidences of diabetes mellitus in the sham-operated male and female rats were 100% and 0%, respectively. Orchiectomy reduced the incidence of diabetes to 20%, whereas ovariectomy increased it to 30%. Administration of sex hormones restored the incidence to 89% in males and 0% in females. In vivo insulin-stimulated glucose uptake as measured with a euglycemic clamp was reduced in sham-operated males, castrated males with hormone replacement (HR), and castrated females without HR as compared with sham-operated females and castrated females with HR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of difference in amount of exercise training on prevention of diabetes mellitus in the Otsuka-Long-Evans-Tokushima fatty rats, a model of spontaneous non-insulin-dependent diabetes mellitus.

Exercise training every day has been shown to be effective in preventing the development of non-insulin-dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty (OLETF)). For determination of whether less vigorous exercise training also has a protective effect against the development of NIDDM in this model, seven male OLETF rats each were assigned to training every other day, every 3 days and every 7 days from 6 to 30 weeks of age. At 30 weeks of age, rats trained every other day, 3 days, 7 days and sedentary rats weighed averages of 547, 548, 603 and 695 g and had abdominal fat deposits of 28, 24, 32 and 72 g, respectively. The mean meterages of running of rats trained every other day, 3 days and 7 days over the whole experimental period were 9630, 5166 and 1685 m/week, respectively. At 30 weeks of age, the cumulative incidence of NIDDM in sedentary rats was 85.7% (6/7), while none of the trained rats became diabetic except for one of rats trained every 7 days. The glucose infusion rate (GIR), an index of insulin sensitivity, in the group trained every 7 days, 60.6 +/- 5.0 mumol.kg-1.min-1, was significantly greater than that in the sedentary group, 21.7 +/- 1.7 mumol.kg-1.min-1. Morphological studies on the pancreas of rats trained every other day and every 3 days showed minimal changes of islets, whereas sections of islets from rats trained every 7 days appeared enlarged and fibrotic, though significantly less so than the islets of sedentary rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glucagon-like peptide-1 (GLP-1) molecular forms in human pancreatic endocrine tumors resemble those in intestine rather than pancreas.

Different glucagon-like peptide-1 (GLP-1) molecular forms are produced in the pancreas and the small intestine by differential processing of proglucagon. In this report, molecular forms of GLP-1 in two human pancreatic endocrine tumors were studied and compared with those in the pancreas and small intestine. A predominant GLP-1 immunoreactive form in the pancreas was eluted at the position of GLP-1(1-36) amide, whereas a predominant immunoreactive form in the ileal mucosa was eluted at the position of GLP-1(7-36) amide. In a glucagonoma, GLP-1 immunoreactive forms corresponding to GLP-1(7-36) amide and GLP-1(7-37) were predominant and immunoreactive forms at the position of GLP-1(1-36) amide and GLP-1(1-37) were minor. In another tumor, an insulinoma, immunoreactive forms were detected at the positions of GLP-1(7-36) amide, GLP-1(7-37), GLP-1(1-36) amide and GLP-1(1-37). Thus, the pattern of GLP-1 molecules in pancreatic tumors was not a pancreatic pattern and mimicked that found in the small intestine or consisted of both the patterns found in the small intestine and the pancreas. These data suggest that neoplastic transformation of the islet cells is associated with a switching in processing phenotype from islet (A) cells to intestinal (L) cells.

Chromatography, High Pressure Liquid↗

Calcium accumulation following middle cerebral artery occlusion in stroke-prone spontaneously hypertensive rats.

Delayed neuronal damage in the ischemic region of the rat brain following middle cerebral artery (MCA) occlusion in stroke-prone spontaneously hypertensive rats was studied. The distribution of neuronal damage was determined by 45Ca autoradiography. Accumulation of 45Ca was observed in the corpus callosum and ipsilateral cerebral cortex immediately following MCA occlusion. After 3 days of occlusion, 45Ca had accumulated in the ipsilateral pyramidal tract, the ventral posterior nucleus of the thalamus, and the lateral portion of the striatum. Significant accumulation of 45Ca was observed in the same areas after 7 and 14 days of occlusion. Next the effect of MK-801 on accumulation of 45Ca after MCA occlusion was examined using the same technique. MK-801 (0.5-10 mg/kg i.v.) or saline was administered 15 min before MCA occlusion, and volumes of accumulation of 45Ca were calculated 1 week after ischemic insults. MK-801 significantly reduced 45Ca uptake in the cortex, striatum, and thalamus. Furthermore, there was a strong statistical correlation between the volume of accumulation of 45Ca in the cortex and that in the thalamus (r = 0.8974; p < 0.001; n = 25). We speculate that delayed neuronal damage in the corpus callosum, ipsilateral pyramidal tract, and thalamus may be caused by secondary neuronal degeneration. However, neuronal damage in the striatum, a segment not supplied by the MCA, may be related to excessive release of glutamate.

Animals↗

Local cerebral blood flow and glucose metabolism in chronic focal ischaemia of stroke-prone spontaneously hypertensive rats.

The relationship between local cerebral blood flow (ICBF) and local cerebral glucose metabolism (ICGU) at the chronic stage of focal cerebral ischaemia was assessed in young stroke-prone spontaneously hypertensive rats (SHRSP) following occlusion of the distal middle cerebral artery (MCA). On day 7 following this occlusion, ICBF and ICGU were measured by autoradiographic methods using 14C-iodoantipyrine and 14C-2-deoxyglucose (2DG), respectively. The infarct was limited to the ipsilateral cerebral cortex. A narrow band of increased uptake of 14C-2DG was observed in the border zone at the periphery of infarcted areas. The ICBF in the ischaemic cortex revealed a graded reduction from the ischaemic centre to the surrounding tissues. A significant reduction in ICGU coupled to CBF was also observed in 4 of 13 selected noninfarcted regions ipsilateral to the MCA occlusion. The ischaemic regions had a significant increase in water content. The region with ischaemic oedema was limited to a narrow area compared with the findings regarding ICBF and ICGU. The SHRSP strain has more severe cerebral ischaemia, oedema formation, and metabolic derangement at the chronic stage of focal ischaemia, compared to normo-tensive animals.

Animals↗

Characterization of vasoactive intestinal peptide receptors on rat alveolar macrophages.

In view of the evidence that vasoactive intestinal peptide (VIP) may modulate acute inflammatory injury in the lung, we investigated the presence and characteristics of VIP receptors on alveolar macrophages (AMs). We examined the binding of monoiodinated [Tyr(125I)10]-labeled VIP (125I-VIP) to rat AMs (> 96% pure), obtained from Sprague-Dawley rats by bronchoalveolar lavage (BAL). At 23 degrees C, the interaction of 125I-VIP with AMs was rapid, reversible, saturable, and linearly proportional to the number of cells. At equilibrium, the binding was competitively inhibited by 10(-11)-10(-6) M of native peptide [half-maximal inhibition (IC50) = 0.53 +/- 0.34 nM, n = 8], with evidence for two classes of binding sites: one with a high affinity (Kd = 0.20 +/- 0.09 nM) and a low capacity (1,190 +/- 640 sites/cell) and another with a low affinity (Kd = 43.2 +/- 13.8 nM) and a high capacity (51,700 +/- 14,000 sites/cell). VIP-related peptides inhibited the binding with the order of potency: VIP > peptide histidine isoleucine > helodermin >> secretin; glucagon was ineffective. In the presence of 3-isobutyl-1-methylxanthine, VIP dose dependently stimulated adenosine 3',5'-cyclic monophosphate accumulation in intact AMs, with maximal stimulation (6.3 times basal level) at 1 nM, and half-maximal accumulation at 0.23 +/- 0.11 nM VIP (Kd for high-affinity sites). For determination of the mass of the VIP receptor, 125I-VIP was covalently bound to AMs with the cross-linking agent dithiobis succinimidyl propionate. Autoradiographic studies after sodium dodecyl sulfate/polyacrylamide gel electrophoresis of solubilized affinity-labeled cells revealed a single major band of M(r) 76,400. We conclude that VIP binds to specific receptors on rat AMs that are coupled to adenylate cyclase, through which VIP may modulate inflammatory responses within the lung.

Animals↗

Giant intracranial aneurysm with rapid thrombus formation and intramural hemorrhage--case report.

A 50-year-old female presented with an unusual giant intracranial aneurysm that showed rapid, spontaneous thrombus formation and subsequent intramural hemorrhage. The thrombus appeared as a homogeneous area on magnetic resonance images, in contrast to the usual heterogeneous appearance. Two months after thrombus formation, the aneurysm had grown and developed intramural hemorrhage. The growth of giant intracranial aneurysms is related to neovascularization and recurrent intramural hemorrhage. The rapid formation of an intra-aneurysmal thrombus may stimulate neovascularization, resulting in intramural hemorrhage and aneurysmal growth.

Basilar Artery↗

The effect of probucol on the development of non-insulin dependent diabetes mellitus in Otsuka Long Evans Tokushima Fatty (OLETF) rats.

The effect of probucol which acts as a scavenger of free radicals, on preventing the development of non-insulin dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) was examined. Sixteen male OLETF rats aged 5 weeks were divided into two groups. One group were fed standard laboratory chow and the other group were fed the chow containing 1% probucol. At 12, 16, 24 weeks of age, an oral glucose tolerance test (OGTT) was performed. At 24 weeks of age, the cumulative incidences of diabetes mellitus in both groups were 100%. After two weeks, insulin-mediated glucose uptake was measured using a euglycemic clamp technique. There was no significant difference in glucose infusion rates between both groups. At the end of the experiment, plasma lipid concentrations were measured. The serum total cholesterol levels were significantly lower in rats fed probucol containing chow (66.3 +/- 3.7 mg/dl) than those of rats fed standard laboratory chow (78 +/- 6.4 mg/dl). On the other hand, the serum triglyceride level were not significantly different between them. Histological studies on the pancreas of both groups showed enlarged fibrotic islets and mononuclear cell infiltration in the periinsular area, though to a modest extent. These results demonstrated that probucol was not effective in preventing the development of NIDDM in this model animal. Considering these data, inflammatory destruction of pancreatic beta cells by free radical may not be involved in the development of NIDDM.

Animals↗

[A case of cutaneous and brain metastasis of gastric carcinoma, treated effectively by chemotherapy with CDDP, MMC, etoposide and 5'-DFUR].

A case of cutaneous and brain metastasis of gastric carcinoma, treated effectively by chemotherapy, is reported. The patient was a 67-year-old female. She underwent total gastrectomy for advanced gastric carcinoma with direct invasion to liver. Six months later, she was admitted with headache and multiple skin nodules on the trunk. CT showed two round tumor shadows on the left side of brain, and a skin biopsy specimen revealed poorly differentiated adenocarcinoma. Chemotherapy with 10mg of CDDP, 2mg of MMC, 150mg of etoposide and 300mg/day of 5'-DFUR was performed. After the third course of chemotherapy, cutaneous and brain metastasis disappeared. Although the patient died of pulmonary metastasis 24 weeks after, cutaneous and brain metastasis disappeared 12 weeks.

Adenocarcinoma↗

[CT findings of pulmonary sarcoidosis].

A retrospective review was performed on CT findings in 46 patients of pulmonary sarcoidosis proven by histology. Pulmonary lesions were detected in 26 patients (56.5%). Frequent CT findings were peribronchial markings (69.2%), diffuse small nodules (65.4%), pleural lesions (38.5%), lymphangitis carcinomatosa like changes (30.8%), and large irregular nodules (30.8%). Follow up CTs were obtained in 18 patients. Peribronchial markings and diffuse small nodules had tendency to improve, although atelectasis, pleural thickening, and bullae were irreversible and progressive. CT plays an important role in the diagnosis and have a prognostic value in pulmonary sarcoidosis.

Adult↗

Cellular mechanism of glyburide-induced insulin gene expression in isolated rat islets.

The cellular mechanism for the effects of glyburide on the synthesis and release of insulin and insulin gene expression in isolated islets was investigated. On incubation for 1 h, glyburide increased insulin release without affecting either the insulin content or the PPI mRNA level. H-7, an inhibitor of PKC, inhibited the glyburide-induced insulin release, while H-8, an inhibitor of cyclic nucleotide-dependent protein kinases, did not affect the glyburide-induced insulin release. On incubation for 20 h, glyburide increased insulin release and the PPI mRNA level, without affecting the insulin content. H-7 inhibited glyburide-induced insulin release and increased the PPI mRNA level. H-8 significantly inhibited both the glyburide-induced increase in insulin release and increase in PPI mRNA level. In conclusion, glyburide stimulated insulin release via a PKC-mediated pathway and increased the PPI mRNA level via cyclic nucleotide-dependent protein kinase(s).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Successful treatment of increased intracranial pressure by barbiturate therapy in a patient with severe sinus thrombosis after failure of osmotic therapy. A case report.

A patient with sinus thrombosis and characteristic magnetic resonance imaging (MRI) findings, who was managed successfully by barbiturate therapy is reported. MRI showed massive high intensity lesions on T2-weighted image which indicated venous cerebral infarction and brain oedema. Intravenous infusion of thiopental decreased increased intracranial pressure (ICP). The effectiveness of barbiturate therapy is discussed in terms of the similarity between this case and experimental sinus thrombosis. Barbiturate therapy should be considered in cases of severe sinus thrombosis with elevated ICP.

Adult↗

Mercury and selenium contents in amyotrophic lateral sclerosis in Hokkaido, the northernmost island of Japan.

We evaluated the pathogenicity of mercury (Hg) and selenium (Se) which are supposed to be one of the risk factors in the development of amyotrophic lateral sclerosis (ALS). Hg and Se contents were measured in plasma, blood cells, scalp hair samples of 21 sporadic ALS patients and 36 controls, who included 19 patients with other neurological diseases, in Hokkaido, the northernmost island of Japan. Hg and Se levels in plasma and blood cells of ALS patients were significantly lower in advanced staged ALS patients than controls. Low Hg and Se contents in ALS, being correlated with their disabilities and nutritional conditions, would rather reflect the disease contracted states than the pathogenic roles in ALS.

Adult↗

Effect of VA-045 on a closed head injury model in rats.

The effect of VA-045, a novel apovincaminic acid derivative, was studied in a model of closed head injury (CHI) in rats. CHI was induced by dropping a 400 g weight through a tube from 70 cm above a steel helmet placed on the vertex. Intravenous administration of VA-045 and thyrotropin-releasing hormone (TRH) reduced both the duration of loss of righting reflex and the duration of disruption of spontaneous movement caused by CHI. VA-045, but not TRH attenuated the CHI-induced decreased step through latency (STL) on a passive avoidance task. Over the same time schedule, however, VA-045 did not attenuate the scopolamine-induced decreased STL. CHI-induced reduction of the amplitude of somatosensory evoked potentials (SEP) was recovered by VA-045 but not by TRH. These findings indicate that VA-045 may be useful for treating patients with CHI-induced disturbance in consciousness.

Animals↗